Bounding Global Aerosol Radiative Forcing of Climate Change.

Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6 W m-2, or -2.0 to -0.4 W m-2 with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds.

Candida catenulata Candidaemia and Possible Endocarditis in a Cirrhotic Patient Successfully De-escalated to Oral Fluconazole.

WHAT IS KNOWN AND OBJECTIVE: Candida catenulata is a fungus commonly found in Australian cheeses. C. catenulata has been identified as the causative pathogen for one report of onychomycosis and one report of candidaemia. CASE DESCRIPTION: A 37-year-old male underwent surgery for an incarcerated umbilical hernia repair and bowel obstruction and presented with severe abdominal pain and ascitic fluid draining from the surgical site. C. catenulata was isolated in blood cultures. The patient was treated with antifungal therapy for approximately 6 weeks. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case describing successful treatment of possible fungal endocarditis caused by C. catenulata.

A review of the public health impacts of unconventional natural gas development.

The public health impact of hydraulic fracturing remains a high profile and controversial issue. While there has been a recent surge of published papers, it remains an under-researched area despite being possibly the most substantive change in energy production since the advent of the fossil fuel economy. We review the evidence of effects in five public health domains with a particular focus on the UK: exposure, health, socio-economic, climate change and seismicity. While the latter would seem not to be of significance for the UK, we conclude that serious gaps in our understanding of the other potential impacts persist together with some concerning signals in the literature and legitimate uncertainties derived from first principles. There is a fundamental requirement for high-quality epidemiological research incorporating real exposure measures, improved understanding of methane leakage throughout the process, and a rigorous analysis of the UK social and economic impacts. In the absence of such intelligence, we consider it prudent to incentivise further research and delay any proposed developments in the UK. Recognising the political realities of the planning and permitting process, we make a series of recommendations to protect public health in the event of hydraulic fracturing being approved in the UK.

Maternal depressive symptoms and early childhood cognitive development: a meta-analysis.

BACKGROUND: Previous findings have been mixed regarding the relationship between maternal depressive symptoms and child cognitive development. The objective of this study was to systematically review relevant literature and to perform a meta-analysis. METHOD: Three electronic databases (PubMed, EMBASE, PsycINFO) were searched. Initial screening was conducted independently by two reviewers. Studies selected for detailed review were read in full and included based on a set of criteria. Data from selected studies were abstracted onto a standardized form. Meta-analysis using the inverse variance approach and random-effects models was conducted. RESULTS: The univariate analysis of 14 studies revealed that maternal depressive symptoms are related to lower cognitive scores among children aged ⩽56 months (Cohen's d = -0.25, 95% CI -0.39 to -0.12). The synthesis of studies controlling for confounding variables showed that the mean cognitive score for children 6-8 weeks post-partum whose mothers had high depressive symptoms during the first few weeks postpartum was approximately 4.2 units lower on the Mental Developmental Index (MDI) of the Bayley Scales of Infant and Toddler Development (BSID) compared with children with non-symptomatic mothers (B̂ = -4.17, 95% CI -8.01 to -0.32). CONCLUSIONS: The results indicated that maternal depressive symptoms are related to lower cognitive scores in early infancy, after adjusting for confounding factors. An integrated approach for supporting child cognitive development may include program efforts that promote maternal mental health in addition to family economic wellbeing, responsive caregiving, and child nutrition.

Treatment of respiratory syncytial virus infection in adult patients with hematologic malignancies based on an institution-specific guideline.

A total of 26 adults with hematologic malignancies and/or hematopoietic stem cell transplant were treated for respiratory syncytial virus (RSV) infection based on an institutional guideline. Thirteen patients received aerosolized ribavirin, and 13 received aerosolized ribavirin and intravenous palivizumab. Two deaths, not attributed to RSV infection, occurred within 90 days of diagnosis.

Sodium content in retail Cheddar, Mozzarella, and process cheeses varies considerably in the United States.

Reducing the sodium content in cheese is expected to contribute to reducing the overall intake of sodium by US consumers. The purpose of this study was to measure the sodium levels in cheeses that are most commonly purchased by US consumers in the retail market, including brand and private label. A secondary purpose of the study was to generate data that can enable the dairy industry to adopt best practices regarding sodium levels in cheeses. The sodium content of a total of 1,665 samples of Cheddar (650 samples), low moisture part skim (LMPS) Mozzarella (746 samples), and process cheese singles (269 samples) from 4 geographical regions were collected over a period of 3 wk, and were analyzed over a 1-mo period. Process cheese contained the highest mean level of sodium (1,242 mg/100g), followed by string cheese (724 mg/100g). Across Cheddar cheese forms and brands, the mean analytical sodium was 615 mg/100g, with 95% between 474 and 731 mg/100g; label sodium ranged from 600 to 800 mg/100g (mean 648 mg). Across all LMPS Mozzarella forms and brands, the mean analytical sodium was 666 mg/100g, with 95% between 452 and 876 mg/100g; label sodium ranged from 526 to 89 3mg/100g (mean 685 mg). Across all process cheese forms and brands, the mean analytical sodium was 1,242 mg/100g, with 95% between 936 and 1,590 mg/100g; label sodium ranged from 1,185 to 1,740 mg/100g (mean 1,313 mg/100g). These findings demonstrate that manufacturers tended to be conservative with their reporting of sodium on labels. Manufacturers need to reduce variability to better target desired sodium levels, which is an opportunity for better process control, and will enable them to label sodium more accurately.

Impact of Aortic Arch Anatomy on Technical Performance and Clinical Outcomes in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Arterial access is a technical consideration of mechanical thrombectomy that may affect procedural time, but few studies exist detailing the relationship of anatomy to procedural times and patient outcomes. We sought to investigate the respective impact of aortic arch and carotid artery anatomy on endovascular procedural times in patients with large-vessel occlusion. MATERIALS AND METHODS: We retrospectively reviewed imaging and medical records of 207 patients from 2 academic institutions who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion from January 2015 to July 2018. Preintervention CTAs were assessed to measure features of the aortic arch and ipsilateral great vessel anatomy. These included the cranial-to-caudal distance from the origin of the innominate artery to the top of the aortic arch and the takeoff angle of the respective great vessel from the arch. mRS scores were calculated from rehabilitation and other outpatient documentation. We performed bootstrap, stepwise regressions to model groin puncture to reperfusion time and binary mRS outcomes (good outcome, mRS ≤ 2). RESULTS: From our linear regression for groin puncture to reperfusion time, we found a significant association of the great vessel takeoff angle (P = .002) and caudal distance from the origin of the innominate artery to the top of the aortic arch (P = .05). Regression analysis for the binary mRS revealed a significant association with groin puncture to reperfusion time (P < .001). CONCLUSIONS: These results demonstrate that patients with larger takeoff angles and extreme aortic arches have an association with longer procedural times as approached from transfemoral access routes.

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software.

BACKGROUND AND PURPOSE: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast. MATERIALS AND METHODS: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study. RESULTS: The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P = .04). CONCLUSIONS: Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

Convolutional Neural Network-Based Automated Segmentation of the Spinal Cord and Contusion Injury: Deep Learning Biomarker Correlates of Motor Impairment in Acute Spinal Cord Injury.

BACKGROUND AND PURPOSE: Our aim was to use 2D convolutional neural networks for automatic segmentation of the spinal cord and traumatic contusion injury from axial T2-weighted MR imaging in a cohort of patients with acute spinal cord injury. MATERIALS AND METHODS: Forty-seven patients who underwent 3T MR imaging within 24 hours of spinal cord injury were included. We developed an image-analysis pipeline integrating 2D convolutional neural networks for whole spinal cord and intramedullary spinal cord lesion segmentation. Linear mixed modeling was used to compare test segmentation results between our spinal cord injury convolutional neural network (Brain and Spinal Cord Injury Center segmentation) and current state-of-the-art methods. Volumes of segmented lesions were then used in a linear regression analysis to determine associations with motor scores. RESULTS: Compared with manual labeling, the average test set Dice coefficient for the Brain and Spinal Cord Injury Center segmentation model was 0.93 for spinal cord segmentation versus 0.80 for PropSeg and 0.90 for DeepSeg (both components of the Spinal Cord Toolbox). Linear mixed modeling showed a significant difference between Brain and Spinal Cord Injury Center segmentation compared with PropSeg (P < .001) and DeepSeg (P < .05). Brain and Spinal Cord Injury Center segmentation showed significantly better adaptability to damaged areas compared with PropSeg (P < .001) and DeepSeg (P < .02). The contusion injury volumes based on automated segmentation were significantly associated with motor scores at admission (P = .002) and discharge (P = .009). CONCLUSIONS: Brain and Spinal Cord Injury Center segmentation of the spinal cord compares favorably with available segmentation tools in a population with acute spinal cord injury. Volumes of injury derived from automated lesion segmentation with Brain and Spinal Cord Injury Center segmentation correlate with measures of motor impairment in the acute phase. Targeted convolutional neural network training in acute spinal cord injury enhances algorithm performance for this patient population and provides clinically relevant metrics of cord injury.

Abnormal Cerebral Perfusion Profile in Older Adults with HIV-Associated Neurocognitive Disorder: Discriminative Power of Arterial Spin-Labeling.

BACKGROUND AND PURPOSE: The aging HIV-infected (HIV+) population has increased vascular comorbidities, including stroke, and increased cognitive deficits compared with the general population. Arterial spin-labeling is a technique to measure cerebral blood flow and is more sensitive than regional volume loss in assessing neurodegenerative diseases and cognitive aging. Previous studies have found global cerebral perfusion abnormalities in the HIV+ participants. In this study, we evaluated the specific regional pattern of CBF abnormalities in older HIV+ participants using quantitative whole-brain arterial spin-labeling. MATERIALS AND METHODS: CBF data from the UCSF HIV Over 60 Cohort and the Alzheimer Disease Neuroimaging Initiative were retrospectively evaluated to identify 19 HIV+ older adults, all with plasma viral suppression (including 5 with HIV-associated neurocognitive disorder); 13 healthy, age-matched controls; and 19 participants with early mild cognitive impairment. CBF values were averaged by ROI and compared among the 3 groups using generalized linear models. RESULTS: When we accounted for age, education, sex, and vascular risk factors, the HIV+ participants demonstrated alterations in regional cerebral perfusion, including hypoperfusion of bilateral temporal, parietal, and occipital brain regions compared with both clinically healthy participants and those with mild cognitive impairment. Arterial spin-labeling showed reasonable test characteristics in distinguishing those with HIV-associated neurocognitive disorder from healthy controls and participants with mild cognitive impairment. CONCLUSIONS: This study found specific CBF patterns associated with HIV status despite viral suppression-data that should animate further investigations into the pathobiologic basis of vascular and cognitive abnormalities in HIV-associated neurocognitive disorders.

MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.

BACKGROUND AND PURPOSE: Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. MATERIALS AND METHODS: Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. RESULTS: Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission (r [9] = -0.78; P = .014) and at 3-month follow-up (r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment (r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. CONCLUSIONS: Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord.

Safety of viral vaccine cell substrates: a reevaluation.

Primary cultures of African green monkey kidney and rabbit kidney as well as diploid cell lines WI-38 and DBS-FRhL-2 were examined for evidence of tumorigenicity and latent RNA tumor viruses. Cells inoculated into immunosuppressed newborn hamsters and rhesus monkeys were not tumorigenic. Cells treated with 2'-deoxy-5-iodouridine to induce the production of latent viruses were examined by electron microscopy, density gradient centrifugation, and the reverse transcriptase enzyme assay. No evidence was found for RNA tumor viruses by the biochemical or biophysical methods used. The results indicated that each type of mammalian cell currently used in the production of virus vaccines would be acceptable for these parameters of safety if similar control procedures were applied at the time the vaccines were manufactured.

Cloning of a cGMP-gated cation channel from mouse kidney inner medullary collecting duct.

The cDNA sequence coding for the cGMP-gated cation channel expressed in the mouse kidney inner medullary collecting duct has been determined. The kidney cGMP-gated cation channel cDNA has an open reading frame of 2055 nucleotides and encodes a 685 amino acid protein. One cDNA clone is alternatively spliced thereby producing a deletion of 107 bp. Two differentially spliced 5' untranslated regions were determined by 5' RACE.

A radioactive antigen-binding assay for the measurement of antibody to Haemophilus influenzae type b capsular polysaccharide.

A new polyethylene glycol (PEG) radioimmunoprecipitation assay was developed for the detection of antibody to Haemophilus influenzae b capsular polysaccharide, polyribosylribitol phosphate (PRP). The radioactive antigen, [3H]PRP, with a high specific activity, was produced by growing the organism in the presence of [3H]ribose and was purified by hydroxylapatite and Sepharose 4B column chromatography. In the assay, PEG (12.5%) was used to separate antibody-bound [3H]PRP from free [3H]PRP. The assay covered the range of 0.5 and 20 ng antibody/assay at a maximum sensitivity of 0.5 approximately 1.0 ng antibody/assay. With various dilutions (1-20 ng antibody/assay) of S. Klein reference antiserum, the within-run coefficient of variation (CV) of 10 replicates ranged from 3.5 to 8.5%. Average CVs of 8.9% and 11.0% were obtained in the between-run and day-to-day reproducibility studies. The binding of [3H]PRP to S. Klein reference antiserum was severely inhibited by a minute amount of non-radioactive PRP; however, no significant interference was found in the presence of high concentrations of polysaccharides from Escherichia coli K100 and Streptococcus pneumoniae indicating that the RIA was highly specific for antibody to H. influenzae b PRP. The present RIA is a simple, specific, sensitive and reproducible procedure for the evaluation of antibody responses of young animals and infants to H. influenzae b vaccines and infections.

Conditioning of morphine-induced taste aversion and analgesia.

The process of selective associations is evident in the aversive conditioning literature, where it has been shown that external cues are readily associated with peripheral pain, whereas taste cues are more easily associated with effects of drug administration. Within this framework, it is of interest that the failures to obtain a conditioned analgesic response to a morphine-associated CS have used external cues as conditioned stimuli. In Experiment 1, subjects re-exposed to a morphine-associated CS not only expressed the anticipated taste aversion, but also exhibited a decrease in pain sensitivity that was evident 15 or 30 min following CS re-exposure. Experiment 2 suggested that the conditioned analgesic response was opioid mediated, as pre-test administration of naloxone blocked expression of the analgesic CR. In Experiment 3, an increase in opiate receptor sensitivity produced by chronic naltrexone treatment did not affect the strength of the taste aversion, but resulted in an increase in the magnitude of the conditioned analgesic response. Collectively, these data suggest a neuropharmacological dissociation in systems mediating the two responses.

Antiperistaltic and isoperistaltic intussusception associated with abnormal motility after Roux-en-Y gastric bypass: a case report.

Antiperistaltic and recurrent intussusceptions are extremely rare in the adult. We report a patient with both. The patient developed an antiperistaltic intussusception distal to her Roux enteroenterostomy years after a Roux-en-Y gastric bypass for morbid obesity. The diagnosis was made preoperatively with gastrointestinal contrast radiography and ultrasonography. At surgery, the intussusception was reduced, and 12 inches of nonviable bowel was resected, with a functional end-to-end anastomosis. An isoperistaltic intussusception occurred in the early postoperative period just distal to the anastomosis. Manometric evaluation of the Roux limb after the second operation showed altered gastrointestinal motility, consisting of orad-propagated and aboard-propagated migrating motor complexes, minimal phase 2 activity, and lack of conversion to the fed pattern with a liquid meal. Although manometry was not performed before the development of the intussusception, our findings are consistent with the hypothesis that altered intestinal motility may contribute to the development of intussusception.

Swim training alters renal and cardiovascular responses to stress in borderline hypertensive rats.

The present study assessed the effects of 40 min of tail shock stress (1-s shock, 0.2 mA every 30 s) on renal and cardiovascular function in swim-trained (T), water-immersed (IM), and untrained (UT) borderline hypertensive rats (BHR). T BHR swam for 2 h/day 5 days/wk for 10-12 wk, whereas IM BHR on the same schedule were placed in water at neck level and were not permitted to swim. Age-matched sedentary controls were paired one each with the exercise group (group 1) and the immersion group (group 2). Heart rate was significantly greater in UT than in T BHR (P = 0.09) during baseline (rest). Heart rate responses during stress were not different between UT and IM BHR (group 2). Systolic and diastolic blood pressures during stress and recovery were not different between UT BHR and T or IM BHR. Urine flow rate was significantly increased from baseline during the first 20 min of stress in UT and IM BHR only. Changes in glomerular filtration rate were not consistent across studies. Renal blood flow decreased significantly from baseline during tail shock stress in UT but not T BHR. Plasma glucose levels were significantly increased above baseline during the second 20 min of stress in UT BHR only and were significantly greater than those in the T BHR. Plasma insulin levels in UT BHR were significantly decreased from baseline during tail shock stress and recovery but were unchanged from baseline in T BHR. These observations suggest that swim training independent of water immersion alters the effect that stress exerts on renal and cardiovascular function in BHR, which results in better fluid and electrolyte conservation in T BHR.

Effects of intratracheal instillation of TNF-alpha on surfactant metabolism.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to play an integral role in the pathogenesis of the acute respiratory distress syndrome. This disorder is characterized by a deficiency of alveolar surfactant, a surface-active material that is composed of key hydrophobic proteins and the major lipid disaturated phosphatidylcholine (DSPC). We investigated how TNF-alpha might alter DSPC content in rat lungs by instilling the cytokine (2.5 microg) intratracheally for 10 min and then assaying parameters of DSPC synthesis and degradation in alveolar type II epithelial cells, which produce surfactant. Cells isolated from rats given TNF-alpha had 26% lower levels of phosphatidylcholine compared with control. TNF-alpha treatment also decreased the ability of these cells to incorporate [(3)H]choline into DSPC by 45% compared with control isolates. There were no significant differences in the levels of choline substrate or choline transport between the groups. However, TNF-alpha produced a 64% decrease in the activity of cytidylyltransferase, the rate-regulatory enzyme required for DSPC synthesis. TNF-alpha administration in vivo also tended to stimulate phospholipase A(2) activity, but it did not alter other parameters for DSPC degradation such as activities for phosphatidylcholine-specific phospholipase C or phospholipase D. These observations indicate that TNF-alpha decreases the levels of surfactant lipid by decreasing the activity of a key enzyme involved in surfactant lipid synthesis. The results do not exclude stimulatory effects of the cytokine on phosphatidylcholine breakdown.

The natural history of intimal flaps in a canine model.

The natural history of arterial intimal flaps has not been well defined. This study characterizes the natural history of unrepaired intimal flaps. Thirty-nine 1-, 2-, and 3-mm hemispheric, distally based intimal flaps were made in 4- to 5-mm diameter canine femoral and carotid arteries. Twenty arteries had 2- and 3-mm intimal flaps and were monitored for short-term arterial thrombosis and flap extension. Nineteen had 1- and 2-mm intimal flaps and were monitored for thrombosis, long-term development of neointimal hyperplasia, arterial stenosis, and persistence of the flap. While 40% of the arteries with 3-mm intimal flaps developed thrombosis in 3 to 5 days, only 3% of the arteries with 1- or 2-mm intimal flaps developed thrombosis. Most 1- to 2-mm intimal flaps resolved and the subsequent development of neointimal hyperplasia or arterial stenosis was minimal. Arteries with hemodynamically significant stenoses from intimal flaps warrant repair, while arteries with smaller intimal flaps may not require repair.